The following is a summary of “Association of the Informant-Reported Memory Decline With Cognitive and Brain Deterioration Through the Alzheimer Clinical Continuum,” published in the June 2023 issue of Neurology by Kuhn, et al.
Limited research exists on the association between informant-reported subjective memory decline (informant report) and Alzheimer’s disease (AD) biomarkers. For a study, researchers sought to investigate the clinical significance of the informant report across the AD clinical continuum by examining its specific relationships with amyloid deposition, cognition, and neurodegeneration.
Participants from two cohorts, the Imagerie Multimodale de la maladie d’Alzheimer à un stade Précoce (IMAP+) primary cohort and the Alzheimer Disease Neuroimaging Initiative (ADNI) replication cohort, were included.
All participants underwent multimodal neuroimaging and neuropsychological assessments. Longitudinal data from IMAP+ participants with follow-up data up to 36 months were also utilized. The informant report was measured using the Cognitive Difficulties Scale (IMAP+) and Everyday Cognition (ADNI). General linear models examined the cross-sectional associations between the informant report and amyloid-PET, cognitive performance, and neurodegeneration (atrophy and hypometabolism) in Alzheimer’s signature areas. Longitudinal associations were assessed using linear mixed-effects models in the IMAP+ cohort.
The IMAP+ cohort comprised 110 participants, including 32 cognitively unimpaired older individuals (controls) with an average age of 70.91 ± 6.57 years (50% females), 25 patients with subjective cognitive decline (SCD) with an average age of 65.88 ± 6.64 years (40% females), 35 with mild cognitive impairment (MCI) with an average age of 72.49 ± 7.5 years (34% females), and 18 with Alzheimer-type dementia (AD dementia) with an average age of 68.17 ± 8.59 years (28% females). The ADNI cohort included 731 participants, including 157 controls with an average age of 74.21 ± 5.95 years (55% females), 84 with SCD with an average age of 72.00 ± 5.41 years (63% females), 369 with MCI with an average age of 71.84 ± 7.4 years (44% females), and 121 with AD dementia with an average age of 74.29 ± 7.75 years (40% females). In the IMAP+ cohort, a higher informant report was strongly associated with greater amyloid-PET, specifically in patients with MCI (β = 0.48, P = 0.003), and lower cognitive performance in patients with SCD (global cognition: β = −0.41, P = 0.04) and MCI (memory: β = −0.37, P = 0.03). These findings in patients with MCI were replicated in the ADNI cohort, with a higher informant report associated with increased amyloid-PET (β = 0.25, P < 0.001) and worse memory performance (β = −0.22, P < 0.001). Associations were also extended to neurodegeneration in AD signature areas (β = −0.2, P < 0.001). Longitudinal analyses in the IMAP+ cohort revealed links between the informant report and global cognitive decline over time in patients with MCI (estimate −0.74, SE 0.26, P = 0.005) and SCD (estimate −0.36, SE 0.26, P = 0.02), where a higher baseline informant report also predicted an increased amyloid-PET over time (estimate 0.008, SE 0.003, P = 0.02).
The results suggested that the informant report was particularly relevant in patients with MCI, strongly associated with higher amyloid-PET, indicating impairment due to AD. The findings highlighted the clinical value of the informant report in assessing AD-related pathology and cognitive decline along the disease continuum.